Hematologic and hemostatic disorders are common causes of hospital admissions, morbidity and mortality. However, these disorders, considered individually, are uncommon, a fact that has made them difficult to study in the context of a health care system in which therapy of rare disorders is not standardized and single institution studies cannot accrue sufficient numbers of patients to reach meaningful conclusions. For this reason, a network of centers to collaboratively study such disorders is needed. In this application, we will pursue two primary goals. First, we will provide an overview of clinical research activity in hemostasis and transfusion medicine at Case Western Reserve University School of Medicine (CWRU)/University Hospitals of Cleveland (UHC), and demonstrate the benefits of including CWRU/UHC in the hemostasis/transfusion medicine clinical research consortium. The strengths of our institution in this regard include 1) the large volume of adult and pediatric patients with congenital and acquired hematologic disorders who receive care here, 2) the CWRU/UHC Cancer Center, an NCI-designated comprehensive cancer center through which a well established clinical research infrastructure is available for administering and monitoring our research activities, and 3) the experience and track record of our faculty in accruing patients to NIH-sponsored clinical trials. Our second goal will be to provide a comprehensive rationale and experimental approach for studying two common thrombocytopenic disorders, heparin-associated thrombocytopenia (HIT) and immune thrombocytopenic purpura (ITP). With regard to HIT, we will assess the incidence of subclinical thrombosis in newly diagnosed patients with HIT and "asymptomatic thrombocytopenia", and evaluate the need for alternative anticoagulation in these patients. We hypothesize that such therapy may not be necessary in all cases. We will also directly compare the efficacy of refludan and argotraban in preventing the development of thrombi in this patient group. In our second project, we will assess the incidence of H. pylori infection in a large cohort of patients with ITP, and determine whether eradication of H. pylori induces a remission of ITP. We hypothesize that many patients with ITP will respond to this intervention. Successful completion of these studies will provide important insights into the management of each of these disorders that will have an important and immediate impact on their management.